The UCLA Center for the Study of Parkinson's Disease will use an integrated multidisciplinary approach to elucidate the effects of nigrostriatal lesions and treatments of Parkinson's disease on the molecular and cellular characteristics of the subthalamic nucleus. This region of the basal ganglia has recently emerged as an important focus for the development of novel therapeutic strategies for the disease. The goal of the Center will be to identify new molecular targets for non-invasive pharmacological treatments for Parkinson's disease. The techniques of molecular neuroanatomy, slice electrophysiology, in vivo microdialysis and behavioral analysis will be used in four animal models: I) rats with nigrostriatal lesions; 2) lesioned rats treated with L-DOPA; 3) lesioned rats with chronic deep brain stimulation of the subthalamic nucleus; 4) lesioned rats with implanted OABA producing cells in the subthalamic nucleus. Key findings will be examined with molecular anatomical techniques in post-mortem human brain. Research in the Center will be supported by an Administrative and Communication core. In addition, an Animals and Neuropathology (Core B), Molecular Biology (Core C), and Neuroengineering (Core D) cores will provide standardized research tools for all projects and develop new cutting edge technology to enhance research in the Center. Core B will provide standardized surgical, behavioral, histological and neurochemical procedures for all the animal models examined in the Center, and will collect well characterized brains form patients with Parkinson's disease for study of the subthalamic nucleus. Core C will provide all projects with GABA-producing cells for in vivo transplantation, and will identify changes in gene expression with DNA microarray technology. Core D will develop and manufacture deep brain stimulation probes for rats and develop miniaturized probes for measuring neurotransmitter release. Interactions between the Center and clinical investigators in the Movement Disorder Program at UCLA will provide an ideal conduit for the rapid translation of research findings into clinical applications. The Center will provide a dynamic training environment that will expand the research capabilities of scientists at all career levels and their trainees. The Center will facilitate the participation of new investigators across the UCLA campus in research on Parkinson's disease and will reinforce the existing interactions between basic and clinical research on Parkinson's disease at UCLA.